Epidemiology of Mucopolysaccharidoses Update

Abstract

Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by a lysosomal enzyme deficiency or malfunction, which leads to the accumulation of glycosaminoglycans in tissues and organs. If not treated at an early stage, patients have various health problems, affecting their quality of life and life-span. Two therapeutic options for MPS are widely used in practice: enzyme replacement therapy and hematopoietic stem cell transplantation. However, early diagnosis of MPS is crucial, as treatment may be too late to reverse or ameliorate the disease progress. It has been noted that the prevalence of MPS and each subtype varies based on geographic regions and/or ethnic background. Each type of MPS is caused by a wide range of the mutational spectrum, mainly missense mutations. Some mutations were derived from the common founder effect. In the previous study, Khan et al. 2018 have reported the epidemiology of MPS from 22 countries and 16 regions. In this study, we aimed to update the prevalence of MPS across the world. We have collected and investigated 189 publications related to the prevalence of MPS via PubMed as of December 2020. In total, data from 33 countries and 23 regions were compiled and analyzed. Saudi Arabia provided the highest frequency of overall MPS because of regional or consanguineous marriages (or founder effect), followed by Portugal, Brazil, the Netherlands, and Australia. The newborn screening is an efficient and early diagnosis for MPS. MPS I has been approved for newborn screening in the United States. After the newborn screening of MPS I, the frequency of MPS I increased, compared with the past incidence rates. Overall, we conclude that the current identification methods are not enough to recognize all MPS patients, leading to an inaccurate incidence and status. Differences in ethnic background and/or founder effects impact on the frequency of MPS, which affects the prevalence of MPS. Two-tier newborn screening has accelerated early recognition of MPS I, providing an accurate incidence of patients.

Automated Assessment of Thoracic-Abdominal Asynchrony in Patients with Morquio Syndrome

“…A simple algorithm, elastic-net, was used for the automated classification task because of the small sample size, and yet the accuracy was high; only one patient’s diagnostic classification did not match the clinical assessment. The data size was small for ML training; however, it was a large data set for a rare disease that occurs in 1 in 200,000 to 300,000 births [ 1 , 2 , 3 ]. Further, since the ICP variable can be used to observe the progression of the patients’ respiratory status over time, it is ideal for monitoring and managing their respiratory function until they are old enough to have a surgery.…”

“…Morquio syndrome (technically termed “mucopolysaccharidosis type IV [MPS IV]”) is a rare disorder that occurs in 1 out of 200,000 to 300,000 births [ 1 , 2 , 3 ]. Individuals with this disorder have a deficiency of a lysosomal enzyme, either N-acetylgalactosamine-6-sulfate sulfatase (GALNS; Morquio A) or β -galactosidase (Morquio B) and cannot break down specific glycosaminoglycans (GAGs).…”

Diagnosis of Mucopolysaccharidoses and Mucolipidosis by Assaying Multiplex Enzymes and Glycosaminoglycans

“…For this reason, it is critical to develop a newborn screening protocol and methodology of MPS that can be implemented in a statewide screening program. This newborn screening program can aid in the detection of disease before clinical signs and symptoms arise [18][19][20][21][22][23][24]. There are currently already over 20 states that have adopted newborn screening for MPS I [25][26][27][28].…”

“…These methods include the internal disaccharide method through enzymatic degradation developed by Oguma et al to analyze GAGs from serum/plasma by utilizing chondroitinase B, keratanase II, and heparitinase enzymes, which digest polysaccharides to DS, KS, and HS disaccharides [37,38]; this method is the most common approach. Since GAG polymers are repeating units of disaccharides, enzymatic degradation results in a single disaccharide [24,39]. Auray-Blais et al developed the methanolysis method followed by LC-MS/MS to identify GAGs (CS, DS, HS, and KS) from the urine of MPS patients [40].…”

“…In the present study, a simultaneous assay method was developed for five GAGs and was applied to newborn screening and for families with a history of LSD [10,11,13,24,[49][50][51]. Moreover, the dried blood spots (DBS) from 43 subjects with clinically suspected MPS or ML were analyzed, and both GAG and enzyme activity levels for MPS I, II, IIIB, IVA, and VI were analyzed.…”